scholarly journals Expedient Microwave-Assisted Synthesis of Bis(n)-lophine Analogues as Selective Butyrylcholinesterase Inhibitors: Cytotoxicity Evaluation and Molecular Modelling

2021 ◽  
Author(s):  
Viktor Câmara ◽  
Ana Julia Soares ◽  
Brunella Biscussi ◽  
Ana Paula Murray ◽  
Isabella Guedes ◽  
...  
Keyword(s):  
Ammonium Acetate ◽  
Docking Studies ◽  
Microwave Assisted Synthesis ◽  
One Pot ◽  
Cytotoxic Effects ◽  
One Step ◽  
The Brain ◽  
Micromolar Range ◽  
Potent Inhibitory Activity

In the brain of patients with chronic Alzheimer’s disease (AD), the butyrylcholinesterase (BuChE) levels rise while the acetylcholinesterase (AChE) levels decrease. Therefore, development of new selective BuChE inhibitors is of vital importance. Here we present a series of bis(n)‑lophine analogues, where two lophine derivatives are connected by a methylene chain. The bis(n)-lophine analogues were synthesized through one-pot four component reaction between pyridinecarboxaldehydes, 1,n-alkanediamines, benzil, and ammonium acetate. The reactions were performed in a microwave reactor in one step for symmetrical bis(n)-lophines, and in two steps for unsymmetrical bis(n)-lophines. The compounds are strongly selective to BuChE, since none of them inhibit AChE. All the compounds, except 7a, 7b and 7c, displayed potent inhibitory activity against BuChE at a micromolar and sub-micromolar range (half maximal inhibitory concentration (IC50) 32.25-0.03 μM). The enzyme kinetic and docking studies suggests that the inhibitor act as a dual binding site inhibitor, binding into the bottom of the gorge and in the peripheral anionic site (PAS) of BuChE cavity. Furthermore, in vitro studies showed that compounds 5b and 12b had no cytotoxic effects in kidney Vero, hepatic HepG2 and C6 astroglial cell lines.

Novel Spiro/non-Spiro Pyranopyrazoles: Eco-Friendly Synthesis, In-vitro Anticancer Activity, DNA Binding, and In-silico Docking Studies

2019 ◽  
Vol 15 (2) ◽  
pp. 257-267 ◽  
Author(s):  
Paritosh Shukla ◽  
Ashok Sharma ◽  
Leena Fageria ◽  
Rajdeep Chowdhury
Keyword(s):  
Anticancer Activity ◽  
Anticancer Agents ◽  
In Silico ◽  
Antimicrobial Agents ◽  
Docking Studies ◽  
Bioactive Molecules ◽  
Microwave Assisted Synthesis ◽  
Binding Affinities ◽  
In Silico Docking

Background: Cancer being a deadly disease, many reports of new chemical entities are available. Pyranopyrazole (PPZ) compounds have also been disclosed as bioactive molecules but mainly as antimicrobial agents. Based on one previous report and our interest in anticancer drug design, we decided to explore PPZs as anticancer agents. To the best of our knowledge, we found that a comprehensive study, involving synthesis, in-vitro biological activity determination, exploration of the mechanism of inhibition and finally in-silico docking studies, was missing in earlier reports. This is what the present study intends to accomplish. Methods: Ten spiro and eleven non-spiro PPZ molecules were synthesized by environment-friendly multicomponent reaction (MCR) strategy. After subjecting each of the newly synthesized molecules to Hep3b hepatocellular carcinoma cell lines assay, we selectively measured the Optical Density (OD) of the most active ones. Then, the compound exhibiting the best activity was docked against human CHK- 1 protein to get an insight into the binding affinities and a quick structure activity relationship (SAR) of the PPZs. Results: The two series of spiro and non-spiro PPZs were easily synthesized in high yields using microwave assisted synthesis and other methods. Among the synthesized compounds, most compounds showed moderate to good anticancer activity against the MTT assay. After performing the absorbance studies we found that the non-spiro molecules showed better apoptosis results and appeared to bind to DNA causing disruption in their structures. Finally, the docking results of compound 5h (having N,Ndimethylamino substituted moiety) clearly showed good binding affinities as predicted by our experimental findings. Conclusion: The paper describes a comprehensive synthesis, in-vitro and docking studies done on new PPZs. The newly synthesized series of spiro and non-spiro PPZs were found to possess antineoplasmic activity as evinced by the studies on hep3b cells. Also, the UV visible absorbance study gave clues to the possible binding of these molecules to the DNA. Docking studies corroborated well with the experimental results. Thus, these new molecules appear to be potential anticancer agents, but further studies are required to substantiate and elaborate on these findings.

scholarly journals Improved in vivo PET imaging of the adenosine A2A receptor in the brain using [18F]FLUDA, a deuterated radiotracer with high metabolic stability

2021 ◽  
Author(s):  
Thu Hang Lai ◽  
Magali Toussaint ◽  
Rodrigo Teodoro ◽  
Sladjana Dukić-Stefanović ◽  
Daniel Gündel ◽  
...  
Keyword(s):  
Specific Binding ◽  
Radiochemical Yield ◽  
Toxicity Study ◽  
In Vivo Evaluation ◽  
One Pot ◽  
Specific Binding Ratio ◽  
Mri Studies ◽  
The Brain

Abstract Purpose The adenosine A2A receptor has emerged as a therapeutic target for multiple diseases, and thus the non-invasive imaging of the expression or occupancy of the A2A receptor has potential to contribute to diagnosis and drug development. We aimed at the development of a metabolically stable A2A receptor radiotracer and report herein the preclinical evaluation of [18F]FLUDA, a deuterated isotopologue of [18F]FESCH. Methods [18F]FLUDA was synthesized by a two-step one-pot approach and evaluated in vitro by autoradiographic studies as well as in vivo by metabolism and dynamic PET/MRI studies in mice and piglets under baseline and blocking conditions. A single-dose toxicity study was performed in rats. Results [18F]FLUDA was obtained with a radiochemical yield of 19% and molar activities of 72–180 GBq/μmol. Autoradiography proved A2A receptor–specific accumulation of [18F]FLUDA in the striatum of a mouse and pig brain. In vivo evaluation in mice revealed improved stability of [18F]FLUDA compared to that of [18F]FESCH, resulting in the absence of brain-penetrant radiometabolites. Furthermore, the radiometabolites detected in piglets are expected to have a low tendency for brain penetration. PET/MRI studies confirmed high specific binding of [18F]FLUDA towards striatal A2A receptor with a maximum specific-to-non-specific binding ratio in mice of 8.3. The toxicity study revealed no adverse effects of FLUDA up to 30 μg/kg, ~ 4000-fold the dose applied in human PET studies using [18F]FLUDA. Conclusions The new radiotracer [18F]FLUDA is suitable to detect the availability of the A2A receptor in the brain with high target specificity. It is regarded ready for human application.

scholarly journals Design, Synthesis and Comprehensive Investigations of Pyrrolo[3,4-d]pyridazinone-Based 1,3,4-Oxadiazole as New Class of Selective COX-2 Inhibitors

2020 ◽  
Vol 21 (24) ◽  
pp. 9623
Author(s):  
Łukasz Szczukowski ◽  
Edward Krzyżak ◽  
Adrianna Zborowska ◽  
Patrycja Zając ◽  
Katarzyna Potyrak ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Docking Studies ◽  
One Pot ◽  
Design Synthesis ◽  
Biological Studies ◽  
Cox 2 ◽  
Anti Inflammatory ◽  
Dna Strand ◽  
Cox 2 Inhibitors

The long-term use of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) in treatment of different chronic inflammatory disorders is strongly restricted by their serious gastrointestinal adverse effects. Therefore, there is still an urgent need to search for new, safe, and efficient anti-inflammatory agents. Previously, we have reported the Mannich base-type derivatives of pyrrolo[3,4-d]pyridazinone which strongly inhibit cyclooxygenase, have better affinity to COX-2 isoenzyme and exert promising anti-oxidant activity. These findings encouraged us to perform further optimization of that structure. Herein, we present the design, synthesis, molecular docking, spectroscopic, and biological studies of novel pyrrolo[3,4-d]pyridazinone derivatives bearing 4-aryl-1-(1-oxoethyl)piperazine pharmacophore 5a,b–6a,b. The new compounds were obtained via convenient, efficient, one-pot synthesis. According to in vitro evaluations, novel molecules exert no cytotoxicity and act as selective COX-2 inhibitors. These findings stay in good correlation with molecular modeling results, which additionally showed that investigated compounds take a position in the active site of COX-2 very similar to Meloxicam. Moreover, all derivatives reduce the increased level of reactive oxygen and nitrogen species and prevent DNA strand breaks caused by oxidative stress. Finally, performed spectroscopic and molecular docking studies demonstrated that new compound interactions with bovine serum albumin (BSA) are moderate, formation of complexes is in one-to-one ratio, and binding site II (subdomain IIIA) is favorable.

scholarly journals One-Pot Microwave-Assisted Synthesis of Carbon Dots and in vivo and in vitro Antimicrobial Photodynamic Applications

2021 ◽  
Vol 12 ◽  
Author(s):  
María Paulina Romero ◽  
Fernanda Alves ◽  
Mirian Denise Stringasci ◽  
Hilde Harb Buzzá ◽  
Heloísa Ciol ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Carbon Dots ◽  
Microwave Assisted Synthesis ◽  
One Pot ◽  
Blue Led ◽  
Led Light ◽  
Microwave Assisted

Graphical AbstractBrief description of the procedures carried out in this study. In vivo and in vitro antibacterial photodynamic therapy (aPDT) studies, where aPDT mediated by C-DOTS and blue LED light against S. aureus was evaluated.

One-step fabrication of functionalized magnetic adsorbents with large surface area and their adsorption for dye and heavy metal ions

2014 ◽  
Vol 43 (30) ◽  
pp. 11637-11645 ◽  
Author(s):  
Jianzhi Wang ◽  
Guanghui Zhao ◽  
Yanfeng Li ◽  
Hao Zhu ◽  
Xiaomen Peng ◽  
...  
Keyword(s):  
Heavy Metal ◽  
Ethylene Glycol ◽  
Surface Area ◽  
Heavy Metal Ions ◽  
Ammonium Acetate ◽  
One Pot ◽  
Electrostatic Stabilization ◽  
Magnetic Adsorbents ◽  
Chloride Hexahydrate ◽  
One Step

Functionalized magnetic adsorbents were synthesized by a facile and surfactant-free one-pot solvothermal approach, using iron(iii) chloride hexahydrate as precursor, ethylene glycol as reducing agent, ammonium acetate, and EDTA-2Na as electrostatic stabilization agent.

scholarly journals Synthesis, Antiproliferative Activity and Molecular Docking Studies of 1,3,5-Triaryl Pyrazole Compound as Estrogen α Receptor Inhibitor Targeting MCF-7 Cells Line

Molekul ◽  
2020 ◽  
Vol 15 (1) ◽  
pp. 18
Author(s):  
Noval Herfindo ◽  
Riska Prasetiawati ◽  
Daniel Sialagan ◽  
Neni Frimayanti ◽  
Adel Zamri
Keyword(s):  
Molecular Docking ◽  
Antiproliferative Activity ◽  
Docking Simulation ◽  
Docking Studies ◽  
Biological Evaluation ◽  
One Pot ◽  
Vitro Assay ◽  
Oxidative Aromatization ◽  
Mcf 7

This research has been successfully synthesized three compounds of 1,3,5-triaryl pyrazole derivatives by two steps reaction. Firstly, pyrazoline (4a-c) compound was obtained by one-pot reaction of aromatic ketones, aldehyde and hydrazine in basic condition. Then, pyrazole (5a-c) compound was obtained by oxidative aromatization of compound 4 in the presense of acetic acid. Chemical structure of predicted molecules was confirmed by FTIR, NMR and HRMS spectroscopy data analysis. Antiproliferative activity of compound 5a-c were evaluated by in vitro assay against MCF-7 cells line and molecular docking simulation against ERα (PDB ID: 3ERT) using MOE 2019. Biological evaluation result showed that pyrazole compounds had weak antiproliferative activity against MCF-7 cells with IC50 were > 1000 µM, whereas the docking studies agrees the result.

scholarly journals In vitro evaluation and molecular docking analysis of potential anticancer compounds from Annona muricata L.

2021 ◽  
Author(s):  
Pichai Nalini ◽  
Kalibulla Syed Ibrahim ◽  
Durairaj Brindha
Keyword(s):  
Molecular Docking ◽  
Docking Studies ◽  
Mass Spectrometry Data ◽  
Annona Muricata ◽  
Anticancer Activities ◽  
Anticancer Compounds ◽  
Cytotoxic Effects ◽  
Standard Drug ◽  
Cytotoxicity Studies

Abstract Annona muricata L. is widely distributed in tropical and subtropical regions around the world. Traditionally this plant has been used as a medicine for multiple ailments including cancer. The present study focussed on the anticancer activities of hydroethanolic extracts of leaves of A. muricata L. on Dalton’s Lymphoma Ascites (DLA) cell line in comparison with standard drug doxorubicin. Cytotoxicity studies have indicated that the phytoconstituents of A. muricata have the ability to selectively target cancer cells (IC50 = 185.585 µg/ml), whereas minimal or negligible cytotoxic effects were observed on normal cells. Gas Chromatography - Mass Spectrometry data revealed the presence of 16 phytoconstituents comprising mainly alkaloids and phenolic compounds. Pharmacokinetic profiling and molecular docking studies using the phytoconstituents were performed in order to gain a better understanding of the putative mechanisms of action leading to the development of improved and affordable therapies.

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